BACKGROUND: Autoimmune attack of the bulbar region of anagen phase hair follicles by CD8+ T cells and Th1 cytokines has been proposed to result in hair loss in alopecia areata (AA). The initiating stimuli are unknown. As interferon-alpha therapy may trigger AA, we propose that type 1 interferons are involved in the induction of disease.OBJECTIVES: To compare lesional scalp from patients with AA with scalp lesions of cutaneous diseases associated with local type 1 interferon-related protein expression.METHODS: Lesional scalp of patients with AA, discoid lupus erythematosus, lichen planopilaris and androgenetic alopecia was examined by immunohistochemistry for expression of the type 1 interferon-inducible myxovirus protein A (MxA), the chemokine receptor CXCR3, and the cytotoxic proteins granzyme B (GrB) and T-cell intracytoplasmic antigen 1 (TiA-1).RESULTS: MxA was expressed in the intradermal and subcutaneous compartments of the hair follicle including sebaceous glands in inflammatory AA similar to lesions of cicatricial alopecia (discoid lupus erythematosus, lichen planopilaris) but not in the epidermal compartment of AA, and not at all in noninflammatory AA or androgenetic alopecia. The location of CXCR3-expressing cells correlated with MxA expression. The inflammatory cells around the hair follicle in AA included a lower number of GrB+ and TiA-1+ cells compared with cicatricial alopecia and demonstrated predominant TiA-1+ expression.CONCLUSIONS: We demonstrate the expression of type 1 interferon-related proteins in the inflammatory lesions of AA. The distribution pattern of the interferon signature and cytotoxicity-associated proteins in AA differs from cicatricial alopecia.